Abstract: Background The prevalence of neonatal inherited metabolic disorders exceeds 0.5%. This study represents the first comprehensive population-wide screening for these conditions in Hainan Province, contributing to the prevention and control of birth defects in the region and establishing diagnostic laboratory capabilities for inherited metabolic diseases. Objective To investigate the incidence of multiple inherited metabolic disorders (IMDs) among newborns in Hainan Province and provide reliable methods and data to support birth defect prevention and control. Methods This study used dried blood spot (DBS) samples collected from heel pricks of newborns born between February and December 2024 across all obstetric healthcare facilities in Hainan Province. Screening was performed using tandem mass spectrometry, and reference ranges for relevant biomarkers were established using the percentile method. Suspected cases were recalled for confirmatory diagnosis via gas chromatography-mass spectrometry (GC-MS) and gene sequencing. Results A total of 84 184 DBS samples from newborns were collected. Using the percentile method, reference ranges for 14 amino acids, 36 acylcarnitines, 1 ketone, 2 adenosines, and 4 lysophosphatidylcholines were established in 29 676 samples, providing the first normative reference data for Hainan Province. Thirty-eight cases of IMDs were diagnosed, yielding an incidence rate of 1/2 215 (38/84 184). Twelve distinct diseases were confirmed, including phenylketonuria (PKU), hypermethioninemia (HMet), multiple sulfatase deficiency (MUSD), citrin deficiency (CD), primary carnitine deficiency (PCD), short-chain acyl-CoA dehydrogenase deficiency (SCADD), carnitine palmitoyltransferase Ⅰ deficiency (CPTⅠ), carnitine-acylcarnitine translocase deficiency (CACT), 3-methylcrotonyl-CoA carboxylase deficiency (MCCD), glutaric acidemia type Ⅰ (GA-Ⅰ), glutaric acidemia type Ⅱ (GA- Ⅱ ), and short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD), with incidence rates ranging widely from 1/84 184 to 1/6 475. PCD (13 cases), SCADD (6 cases), and CD (5 cases) ranked as the three most prevalent disorders. 42 mutation sites across 12 genes were identified. Conclusion This study establishes the first reference ranges for newborn IMD screening in Hainan Province, providing critical reference criteria for subsequent screening programs. Following the implementation of a comprehensive free screening initiative, the data revealed a relatively high incidence of IMDs in Hainan newborns, with notable genetic complexity and diversity. Disorders of fatty acid metabolism-PCD, SCADD, and CD-were the most frequently detected. These findings underscore the importance of expanded newborn IMD screening in Hainan Province for the prevention and control of birth defects.

Key words: Neonatal screening, Inherited metabolic disorders, Dried blood spots, Incidence rate, Newborn screening, Hainan Province

摘要： 背景 我国新生儿遗传代谢病的患病率在0.5%以上，本研究首次在海南省全域内进行新生儿遗传代谢病的筛查，有助于海南省的出生缺陷防控，为遗传代谢病的诊断提供实验室检测手段。目的 探索海南省新生儿多种遗传代谢病发病情况，为海南省出生缺陷防控提供可靠的方法和参考依据。方法 以2024年2—12月出生在海南省各助产医疗机构的新生儿足跟血干血斑为样本，筛查采用串联质谱法，并利用百分位定位法计算相关检测指标参考范围。疑似样本召回使用气相质谱法及测序法进行诊断验证。结果 共收集到84 184例新生儿足跟血干血斑样本。利用百分位定位法在29 676例样本中计算出了14种氨基酸、36种肉碱、1种酮、2种腺苷和4种溶血卵磷脂的海南省新生儿参考范围。诊断新生儿多种遗传代谢病38例，发病率为1/2 215（38/84 184）。确诊疾病12种：苯丙酮尿症（PKU）、高甲硫氨酸血症（HMet）、枫糖尿病（MUSD）、希特林蛋白缺乏症（CD）、原发性肉碱缺乏症（PCD）、短链酰基辅酶脱氢酶缺乏症（SCADD）、榈酰肉碱转移酶缺乏症I型（CPT Ⅰ）、肉碱酰基转移酶缺乏症（CACT）、3-甲基巴豆酰辅酶A羧化酶缺乏症（MCCD）、戊二酸血症Ⅰ型（GA-Ⅰ）、戊二酸血症Ⅱ型（GA-Ⅱ）、2-甲基丁酰甘氨酸尿症（SBCADD），发病率1/84 184~1/6 475，差异较大。检出病种的前三位依次为PCD（13例）、SCADD（6例）和CD（5例）。检出12个基因共42个位点突变。结论 首次确定了海南省新生儿多种遗传代谢病筛查的正常参考范围，为后续遗传代谢病筛查提供了判定指标，实施全面免费筛查后首次确定了海南省新生儿多种遗传代谢病发病率较高，且基因复杂多样，以脂肪酸代谢障碍的PCD、SCADD、CD较为多见。新生儿多种遗传代谢病筛查在海南出生缺陷防控具有重要意义。

关键词: 新生儿筛查, 遗传代谢病, 干血斑, 发病率, 新生儿疾病筛查, 海南省